A Novel Mouse Model of Advanced Diabetic Kidney Disease
作者： Jean-Francois Thibodeau , Chet E. Holterman , Dylan Burger , Naomi C. Read , Timothy L. Reudelhuber
DOI: 10.1371/JOURNAL.PONE.0113459
关键词: Diabetes mellitus 、 Endocrinology 、 Streptozotocin 、 Internal medicine 、 Renal function 、 Pathology 、 Diabetic nephropathy 、 Fibrosis 、 Tubulointerstitial fibrosis 、 Type 1 diabetes 、 Albuminuria 、 Medicine 、 General Biochemistry, Genetics and Molecular Biology 、 General Agricultural and Biological Sciences 、 General Medicine
摘要: Currently available rodent models exhibit characteristics of early diabetic nephropathy (DN) such as hyperfiltration, mesangial expansion, and albuminuria yet features late DN (hypertension, GFR decline, tubulointerstitial fibrosis) are absent or require a significant time investment for full phenotype development. Accordingly, the aim present study was to develop mouse model advanced with hypertension superimposed (HD mice). Mice transgenic human renin cDNA under control transthyretin promoter (TTRhRen) were employed angiotensin-dependent hypertension. Diabetes induced in TTRhRen mice through low dose streptozotocin (HD-STZ mice) by intercrossing OVE26 (HD-OVE Both HD-STZ HD-OVE displayed more pronounced increases urinary albumin levels compared their littermates. Additionally, HD renal hypertrophy, glomerular scarring evidence fibrosis. showed decline FITC-inulin clearance decreased hyperfiltering STZ OVE mice. Taken together our results suggest that represent robust type I recapitulates key disease which may be studying pathogenesis assessment putative therapeutics.
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